46 research outputs found

    Characterization of glycan determinants that mediate recognition of the major Wuchereria bancrofti circulating antigen by diagnostic antibodies

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    The Global Program to Eliminate Lymphatic Filariasis (GPELF) relies heavily on a rapid diagnostic test (RDT) to a Wuchereria bancrofti circulating filarial antigen (Wb-CFA) to identify endemic areas and for determining when mass drug administration can stop. The antigen contains a carbohydrate epitope that is recognized by monoclonal antibody AD12. Og4C3, a monoclonal antibody that is used in a commercial ELISA for Wb-CFA recognizes the same moiety. Despite its diagnostic importance, little is known about the structure and function of this AD12 epitope . It is also present on other W. bancrofti glycoproteins and on glycoproteins of other filarial worms, but such antigens are not detected in the sera of individuals with most other filarial infections. We report here functional and biochemical analyses that shed light on the interaction between filarial glycoproteins and AD12 and/or Og4C3. Binding of these monoclonal antibodies to a mammalian glycan array suggests the reactive moiety has structural similarity to terminal β-d-glucuronic acid in a 1-3 linkage to other hexoses. However, sera collected from individuals with patent W. bancrofti infection had very low or undetectable serum antibodies to the GlcA-containing array glycans. Unlike other filarial glycoproteins, the Wb-CFA is relatively resistant to protease digestion by pronase and trypsin and completely resistant to the mucinase O-sialoglycoprotein endopeptidase (OSGE). The protease resistance of the Wb-CFA may contribute to its consistent detection in Wb-infected sera

    Views of institutional leaders on maintaining humanism in today’s practice

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    Objective To explore leadership perspectives on how to maintain high quality efficient care that is also person-centered and humanistic. Methods The authors interviewed and collected narrative transcripts from a convenience sample of 32 institutional healthcare leaders at seven U.S. medical schools. The institutional leaders were asked to identify factors that either promoted or inhibited humanistic practice. A subset of authors used the constant comparative method to perform qualitative analysis of the interview transcripts. They reached thematic saturation by consensus on the major themes and illustrative examples after six conference calls. Results Institutional healthcare leaders supported vision statements, policies, organized educational and faculty development programs, role modeling including their own, and recognition of informal acts of kindness to promote and maintain humanistic patient-care. These measures were described individually rather than as components of a coordinated plan. Few healthcare leaders mentioned plans for organizational or systems changes to promote humanistic clinician-patient relationships. Conclusions Institutional leaders assisted clinicians in dealing with stressful practices in beneficial ways but fell short of envisaging systems approaches that improve practice organization to encourage humanistic care

    Genome modeling system: A knowledge management platform for genomics

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    In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms

    Gender-Associated Genes in Filarial Nematodes Are Important for Reproduction and Potential Intervention Targets

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    Lymphatic filariasis is a neglected tropical disease that is caused by thread-like parasitic worms that live and reproduce in lymphatic vessels of the human host. There are no vaccines to prevent filariasis, and available drugs are not effective against all stages of the parasite. In addition, recent reports suggest that the filarial nematodes may be developing resistance to key medications. Therefore, there is an urgent need to identify new drug targets in filarial worms. The purpose of this study was to perform a genome-wide analysis of gender-associated gene transcription to improve understanding of key reproductive processes in filarial nematodes. Our results indicate that thousands of genes are differentially expressed in male and female adult worms. Many of those genes are involved in specific reproductive processes such as embryogenesis and spermatogenesis. In addition, expression of some of those genes is suppressed by tetracycline, a drug that leads to sterilization of adult female worms in many filarial species. Thus, gender-associated genes represent priority targets for design of vaccines and drugs that interfere with reproduction of filarial nematodes. Additional work with this type of integrated systems biology approach should lead to important new tools for controlling filarial diseases

    Mechanical Bonds and Topological Effects in Radical Dimer Stabilization

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    While mechanical bonding stabilizes tetrathiafulvalene (TTF) radical dimers, the question arises: what role does topology play in catenanes containing TTF units? Here, we report how topology, together with mechanical bonding, in isomeric [3]- and doubly interlocked [2]catenanes controls the formation of TTF radical dimers within their structural frameworks, including a ring-in-ring complex (formed between an organoplatinum square and a {2+2} macrocyclic polyether containing two 1,5-dioxynaphthalene (DNP) and two TTF units) that is topologically isomeric with the doubly interlocked [2]catenane. The separate TTF units in the two {1+1} macrocycles (each containing also one DNP unit) of the isomeric [3]catenane exhibit slightly different redox properties compared with those in the {2+2} macrocycle present in the [2]catenane, while comparison with its topological isomer reveals substantially different redox behavior. Although the stabilities of the mixed-valence (TTF2)^(•+) dimers are similar in the two catenanes, the radical cationic (TTF^(•+))_2 dimer in the [2]catenane occurs only fleetingly compared with its prominent existence in the [3]catenane, while both dimers are absent altogether in the ring-in-ring complex. The electrochemical behavior of these three radically configurable isomers demonstrates that a fundamental relationship exists between topology and redox properties

    The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

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    Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data

    Intervenir sobre la cultura organizacional: ¿qué aspectos se pueden considerar?

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    La cultura organizacional (co) es un macroconstructo que involucra una gran variedad de componentes y funciones organizacionales (Warner, 2014). Reyes y Moros (2018) señalan que tiene su origen en el estudio realizado en Hawthorne por Elton Mayo y otros investigadores de la Escuela de las Relaciones Humanas de la Administración, en el que buscaban identificar la influencia de las condiciones físicas y ambientales en el desempeño individual. Para Reyes y Moros (2018), la co se siguió desarrollando en los años setenta con Pettigrew, para ser entendida como un sistema de significados que tanto pública como colectivamente es aceptado para operar en un tiempo y por un grupo determinado. Los autores la definen como “… un sistema de significados compartidos por los miembros de la organización, los cuales son el resultado de una construcción social constituida a través de símbolos y como tal deben ser interpretados”1a edició

    Mechanical Bonds and Topological Effects in Radical Dimer Stabilization

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